Table I.

RA and OA studies considering comorbidity and HRQOL

Reference / Year	*Method	Location	Source of data	Study type	Sample size	HRQOL measures	Comorbidity treatment	Main comorbidity findings/results
RA Studies
Wolfe F, Michaud K, Li T, et al. (22) /2010	3	US	Rheumatology practices	Longitudinal	13,722 with RA	EQ-5D	Self-reported comorbidities, asked about 22 “health problems”; created summary variables and composite index	EQ-5D quality of life score decreased by about 0.04 units for RA. Regardless of comorbid condition, current comorbidity always resulted in a lower EQ-5D score than lifetime comorbidity.
Lee T-J, Park BH, Son HK, et al. (23) /2012	1	Seoul, South Korea	Rheumatology clinic	Cross-sectional; Face-to-face interview survey	196 RA patients	KEQ-5D	Dichotomised comorbidity; assessment of comorbidities not outlined	Patients with comorbidity had lower HRQOL scores than did those without.
Radner H, Smolen JS, Aletaha D. (24) /2011	3	Vienna, Austria	Outpatient clinic	Longitudinal; chart review	380 RA patients with established RA	SF-36	Age-adjusted Charlson Comorbidity Index (CCIA)	Significant (p<0.03) increase of disability within each domain of HAQ with increasing level of comorbidity. Similar results were observed using the physical component score (p=0.003) of the SF-36 and its domains, whereas mental component score (p=0.31) and its domains were unaffected by comorbidities.
Rupp I, Boshuizen HC, Jacobi CE, et al.. (25) /2004	1	Amsterdam, The Netherlands	Outpatient center for rheumatology and rehabilitation	Follow-up study	679 patients with RA	RAND-36	Self-administered questionnaire including 17 chronic diseases; asked whether they had had any of the conditions of the list in the previous 12 months.	The effect of comorbidity on HRQOL depended on both the type of comorbid condition and the dimension of HRQOL. Gastrointestinal (GI) diseases, cancer, dizziness with falling (and less severe chronic pulmonary disease and heart complaints) resulted in significant adverse changes in HRQOL. For the other conditions under study no influence could be detected.
Crilly MA, Johnston MC, Black C. (26) /2013	2	Scotland, United Kingdom	Clinic patients	Cross-sectional; Interviews and medical records checks	114 ambulatory RA patients	EQ-5D	Medical records were reviewed by a rheumatologist for co-existing conditions.	EQ-5D scores were inversely correlated with the overall number of co-existing conditions (Spearman’s q −0.31, p=0.001), number of comorbidities (q −0.22, p=0.02). There was a linear trend of lower EQ-5D with increasing number of co-existing conditions (p=0.003). EQ-5D was −0.18 (95% Cl −0.33 to −0.02) lower in the presence of more than two coexisting conditions compared to none.
Krishnan E, Hakkinen A, Sokka T, et al. (27) /2005	2	Central Finland District, Finland	Finnish population registry	Retrospective; record review	1530 adults with RA	Global assessment of general hedth	Self- reported comorbidities.	Outcomes worsened steadily with increasing number of comorbidities. Number of comorbidities was a statistically significant correlate of general health.
OA Studies
Hopman W, Harrison M, Coo H, et al. (13) /2009	1	Ottawa, Canada	Examined data collected in 10 studies	Retrospective; Interviews and chart reviews	366 with OA	SF-36 or SF-12	Only two comorbidities (cardiovascular disease, diabetes) plus a category of “additional comorbidities” (i.e. defined as yes/no) could be drawn from databases	Comorbid conditions were associated with poorer HRQOL.
Hosseini K, Gaujoux-Viala C, Coste J, et al. (28) /2012	2	Paris, France	Random sample of households; clinical confirmation of diagnosis	Cross-sectional; Population-based survey	878 OA patients	SF-6D from the MOS36-item SF-36	Functional Comorbidity Index; Used comorbidity count and categories (grouped the 18 conditions of this index into nine categories)	For each additional co-morbidity (range 0–9), the mean utility score decreased 0.03 point (beta = - 0.03, p<0.0001)
Tuominen U, Blom M, Hirvonen J, et al. (29) /2007	1	Helsinki, Finland	Orthopaedic patients from 4 hospitals	Cross-sectional	893 OA patients	Generic 15D and VAS	Comorbidities considered dichotomously and collected from the patients’ reported co-morbidities as diagnosed by a medical doctor	The mean number of co-morbidities among the patients was two. Comorbidity was significantly associated with a reduced HRQOL.
Salaffi F, Carotti M, Stancati A,et al. (30) /2005	2,3	Italy	Department of Rheumatology	Cross-sectional; survey	264 OA patients	SF-36	Number of comorbidities and study generated comorbidity index score	There was a significant inverse association with measures of comorbidity (number of comorbidities and comorbidity index score) and both physical and mental SF-36 summary scores.
Combined OA & RA Study
Dominick K, Kelli L, Ahern F, et al. (17) /2004	3	Pennsylvania, United States	State-wide sample enrolled in Pharm Assistance Contract for the Elderly	Cross-sectional; mailed surveys	41,467 older adults with RA and OA	CDC’s Core and Optional HRQOL Modules	Outpatient visit (Medicare Part B) records Charlson Comorbidity Score	Analysis of relationship of comorbidity to HRQOL used combined OA and RA arthritis sample. Among individuals with arthritis those with greater numbers of comorbid illnesses were significantly more likely to report fair or poor general health and to have poorer scores on one or more of the “days” HRQOL items.

^*Method used to measure comorbidity: 1) considered individuals as either having or not having a comorbid condition; 2) used simple counts of diseases in each individual (e.g. patient self-report or chart review); and, 3) used indices including count, weighting conditions and/or assigning severity to assess comorbidity burden.